2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells.

Background: Signal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. Therefore, STAT3 has been validated as a novel anti-cancer drug target and the strategies targeting HCC CSCs may bring new hopes to HCC therapy.

Synthesis of Biotinylated 2-methoxystypandrone and Identification of JAK2 and IKK as its Targets.

Background: 2-Methoxystypandrone (2-MS), isolated from the roots of Polygonum cuspidatum, is a potent dual inhibitor of the STAT3 and NF-κB pathways.

Objective: To investigate the molecular targets and mechanisms of 2-MS.

Method: A biotin-conjugated 2-MS analog, named 2-MS-Biotin, was designed and synthesized.

[GC-MS analysis and cytotoxic activity of the supercritical extracts from roots and stems of Zanthoxylum nitidum].

The volatile components of roots and stems of Zanthoxylum nitidum were investigated by supercritical fluid carbon dioxide extraction (SFE-CO2) and gas chromatography-mass spectrometry(GC-MS). Thirty-one and fifty-one compounds were identified in the supercritical extracts from roots and stems of Z. nitidum, respectively, and total twenty-seven compounds were the common constituents.

2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-κB signaling by inhibiting Janus kinase 2 and IκB kinase.

Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) or the nuclear factor-κB (NF-κB) pathway occurs frequently in cancer cells and contributes to oncogenesis. The activation of Janus kinase 2 (JAK2) and IκB kinase (IKK) are key events in STAT3 and NF-κB signaling, respectively. We have identified 2-methoxystypandrone (2-MS) from a traditional Chinese medicinal herb Polygonum cuspidatum as a novel dual inhibitor of JAK2 and IKK.